Biomedical subjects

H Jiang

Publications and source records attributed to H Jiang.

688 records · Page 39Linked to original sources

PubMedDate not supplied

Signaling mechanisms mediating BDNF modulation of synaptic plasticity in the hippocampus.

Although recent studies indicate that brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal synaptic plasticity, the underlying signaling mechanisms remain largely unknown. Here, we have characterized the signaling events that mediate the BDNF modulation of high-frequency synaptic transmission. Mitogen-associated protein kinase (MAPK), phosphotidylinositol-3 kinase (PI3K), and phospholipase C-gamma (PLC-gamma) are the three signaling pathways known to mediate neurotrophin signaling in other systems. In neonatal hippocampal slices, application of BDNF rapidly activated MAPK and PI3K but not PLC-gamma. BDNF greatly attenuated synaptic fatigue at CA1 synapses induced by a train of high-frequency, tetanic stimulation (HFS). Inhibition of the MAPK and PI3K, but not PLC-gamma, prevented the BDNF modulation of high-frequency synaptic transmission. Neurotrophin-3 (NT-3), a close relative of BDNF, did not activate MAPK or PI3K and had no effect on synaptic fatigue in the neonatal hippocampus. Neither forskolin, which activated MAPK but not PI3 kinase, nor ciliary neurotrophic factor (CNTF), which activated PI3K but not MAPK, affected HFS-induced synaptic fatigue. Treatment of the slices with forskolin together with CNTF still had no effect on synaptic fatigue. Thus, although the activation of MAPK and PI3K is required, the two together are not sufficient to mediate the BDNF effect. Inhibition of new protein synthesis by anisomycin or cycloheximide did not prevent the BDNF effect. These data suggest that BDNF modulation of high-frequency transmission is independent of protein synthesis but requires MAPK and PI3K and yet another signaling pathway to act together in the hippocampus.

Animals↗

PubMedDate not supplied

Current understanding of the molecular basis of chloroquine-resistance in Plasmodium falciparum.

Chloroquine (CQ) is the most successful antimalarial drug ever discovered. Unfortunately, parasites resistant to the drug eventually emerged after its large scale use and are now widespread. Although great progress in our understanding of the mechanisms of CQ action and CQ resistance (CQR) has been achieved over the past two decades, including the identification of the molecules responsible for CQR (e.g., Plasmodium falciparum chloroquine resistant transporter, PfCRT) many questions remain unanswered. Here we highlight recent advances in our understanding of the genetics and molecular mechanisms of CQR, with particular emphasis on the role of genes such as pfcrt and pfmdr1 in the resistance to CQ and other drugs. New drug development and applications will undoubtedly benefit from a better understanding of CQR, eventually leading to more effective malaria control measures.

Animals↗

PubMedDate not supplied

Genetic susceptibility to lung cancer as determined by lymphocytic chromosome analysis.

Chromosomal anomalies were analyzed in the lymphocyte cultures among 96 untreated lung cancer patients and 74 clinically normal comparison subjects. The analysis revealed that >15% of the lung cancer patients showed structural or numerical rearrangements in chromosomes 1,3,5,7,9,12,14, and 21. A case control comparison showed that these aberrations were significantly higher in chromosome 7 [odds ratio (OR) = 2.32; 95% confidence interval (CI), 1.14 and 4.82], chromosome 9 (OR = 2.61; 95% CI, 1.27 and 5.48), chromosome 12 (OR = 4.10; 95% CI, 1.40 and 14.54), and chromosome 21 (OR = 7.75; 95% CI, 1.73 and 70.80) of the patients than in the controls. However, only chromosome 9 (OR = 3.57; 95% CI, 1.33 and 9.46) and chromosome 21 (OR = 6.94; 95% CI, 3.15 and 9.98) retained significance after stratifying on smoking status. Among the lung cancer patients, the breakpoints cluster in specific regions of some of these chromosomes. These regions are 1p13-q21, 3q21-q13, 7p12-q12, 7q12-q12,7q22, 7q32, 9p13-q13, 12p13, 14q11, and 14q32. The distribution of lung cancer patients, according to histological types, showed that aberrations in chromosomes 1,7, and 9 dominated the scenario of chromosomal changes in non-small cell lung carcinomas. Thus, the data on lymphocytic chromosomal rearrangements in lung cancer patients not only indicate the importance of specific genetic changes in the etiology of lung cancer but also emphasizes the putative role of such analysis in determining primary genetic abnormalities in the large heterogeneous group of lung cancers.

Case-Control Studies↗

PubMedDate not supplied

Vanadium(IV) causes 2'-deoxyguanosine hydroxylation and deoxyribonucleic acid damage via free radical reactions.

Vanadium(IV) caused molecular oxygen dependent 2'-deoxyguanosine (dG) hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15-minute incubation of 1.0 mM dG and 1.0 mM VOSO4 (vanadium(IV)) in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31 percent. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Diethylenetriaminepentaacetic acid (DTPA) and deferoxamine blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen dependent deoxyribonucleic acid (DNA) strand breaks in a pattern similar to that observed for dG hydroxylation. Reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA strand breaks. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks.

Chelating Agents↗